Crovace et al. 2010). In contrast, a different model based on acute
mechanical disruption of the tendon core failed to show the benefit of
implanted stem cells over controls of BM supernatant (Caniglia et al. 2012),
although this study only evaluated ultrastructure at one early (12- week) timepoint with no mechanical or functional evaluation. However, experimental
models using induced acute injuries have limitations as they do not reflect all
the features of clinical disease, which commonly has a preceding phase of
age-related degeneration.
The clinical efficacy of MSCs was recently reported in an adequately-powered
large study of SDFT injuries in Thoroughbred racehorses treated with
autologous MSCs in bone marrow supernatant (Godwin et al. 2012). The
authors demonstrated significantly reduced re-injury rates compared to two
published case series of horses with SDFT injuries, which had undergone a
variety of other treatments (Dyson 2004 ; O’Meara 2010). However, there was
no contemporaneous control population and no indication of a mechanism for
the action of implanted MSCs on the healing of the damaged tendon matrix.
More recently still, in another study horses with career-ending naturallyoccurring superficial digital flexor tendon injury were allocated randomly to
MSC-treatment and control groups (Smith et al. 2013). Following a 6 month
exercise programme tendons were assessed for structural stiffness by nondestructive mechanical testing and for morphological and molecular
composition.
The treated tendons exhibited statistically significant
improvements in all parameters compared to saline-injected control tendons
towards that of normal tendons and those in the contralateral limbs.
Specifically, in comparison to saline-treated tendons, the treated tendons had
significantly improved elasticity (p<0.05), lower (improved) histological scoring
of organisation and crimp pattern (p<0.001 and p<0.05 respectively), lower
cellularity (p<0.002), DNA content (p<0.05), vascularity (p<0.03), water
content (p<0.05), GAG content (p<0.05), and MMP-13 activity (p<0.02). The
authors concluded that treatment with autologous MSCs in marrow
supernatant therefore provides significant benefits compared to untreated
tendon repair in enhancing the normalisation of biomechanical, morphological,
and compositional parameters.
Mesenchymal stem cells have also have been used to treat joint lesions via
intra-articular administration. When tested in an equine OA model, injection of
MSCs resulted in a significant improvement in PGE2 level with bone marrow
derived MSCs while there was a significant increase in TNFa level with fat
derived MSCs (Frisbie et al. 2009). The most common intra-articular use has
been for the treatment of meniscal lesions in the equine femorotibial joints,
which carry a poor long-term prognosis, based on positive effects
demonstrated for an experimental menisectomy model in the goat (Murphy et
al. 2003). Reportedly treatment of soft tissue injuries in the femorotibial joint
with arthroscopy and concurrent intra-articular injections of MSCs has
produced unexpectedly favourable results (Frisbie and Stewart 2011; Ferris et
al. 2009), though no controlled studies are as yet available to determine
whether outcome is improved after intra-articular MSC treatment compared to
other treatments.
15-‐18
February
2016
East
London
Convention
Centre,
East
London,
South
Africa
183